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Pre-existing frontal lobe dysfunction signs as predictors of subsequent neurotoxicity in CAR T cell therapy: insights from a case series.
Fontanelli, Lorenzo; Pizzanelli, Chiara; Milano, Chiara; Cassano Cassano, Raffaella; Galimberti, Sara; Rossini, Maria Ida; Santo, Ignazio; Turco, Francesco; Bonanni, Enrica; Siciliano, Gabriele; Orciuolo, Enrico; Baldacci, Filippo.
Affiliation
  • Fontanelli L; Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
  • Pizzanelli C; Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy. c.pizzanelli@ao-pisa.toscana.it.
  • Milano C; Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
  • Cassano Cassano R; Department of Clinical and Experimental Medicine, Haematology Unit, University of Pisa, Pisa, Italy.
  • Galimberti S; Department of Clinical and Experimental Medicine, Haematology Unit, University of Pisa, Pisa, Italy.
  • Rossini MI; Department of Clinical and Experimental Medicine, Haematology Unit, University of Pisa, Pisa, Italy.
  • Santo I; Department of Clinical and Experimental Medicine, Haematology Unit, University of Pisa, Pisa, Italy.
  • Turco F; Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
  • Bonanni E; Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
  • Siciliano G; Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
  • Orciuolo E; Department of Clinical and Experimental Medicine, Haematology Unit, University of Pisa, Pisa, Italy.
  • Baldacci F; Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
Neurol Sci ; 44(9): 3291-3297, 2023 Sep.
Article de En | MEDLINE | ID: mdl-37160803
ABSTRACT

BACKGROUND:

Chimeric Antigen Receptor (CAR) T cell therapies are innovative treatments against hematological malignancies, with increasing therapeutic indications. Despite their great efficacy, these therapies are hampered by high rates of neurotoxicity (immune effector cell-associated neurotoxicity (ICANS)). In the past few years, several risk factors have been associated with ICANS and grouped together in the attempt to build validated models able to predict neurologic complications. However, little is known about pre-existing neurologic conditions possibly related to the development of neurotoxicity. METHODS AND

RESULTS:

In our case series, including sixteen consecutive patients treated with CAR T cells, we observed that (i) neurotoxicity only occurred in the two patients who presented subtle clinical signs of frontal lobe impairment at baseline and (ii) neurologic manifestations of ICANS consisted of language disturbances and cortical frontal myoclonus, which were both manifestations of a frontal predominant dysfunction.

DISCUSSION:

Based on our experience, we suggest that a pre-existing frontal lobe impairment, even if at a subclinical level, may eventually drive to ICANS, which in turn shows symptoms compatible with a frontal encephalopathy. It is remarkable that this focal neurotoxicity involved the same CNS regions that were responsible of subtle neurological signs at baseline. Future studies on larger numbers of patients are needed to confirm the possible role of baseline frontal lobe dysfunction as a predictor of ICANS, in order to enhance efforts to safely deliver CAR T cell therapy.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Immunothérapie adoptive / Syndromes neurotoxiques Type d'étude: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limites: Humans Langue: En Journal: Neurol Sci Sujet du journal: NEUROLOGIA Année: 2023 Type de document: Article Pays d'affiliation: Italie

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Immunothérapie adoptive / Syndromes neurotoxiques Type d'étude: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limites: Humans Langue: En Journal: Neurol Sci Sujet du journal: NEUROLOGIA Année: 2023 Type de document: Article Pays d'affiliation: Italie